Urine neutrophil gelatinase-associated lipocalin levels predict acute kidney injury in acute decompensated heart failure patients

Abstract

Background: Acute heart failure (HF) syndromes are frequently complicated with cardiorenal syndromes. The aim of this study was to evaluate the performance of admission neutrophil gelatinase associated lipocalin (NGAL) levels to predict diuretic dose requirement and to predict the occurrence of acute kidney injury (AKI) in patients presenting with acute decompensated HF. Methods: Patients admitted with HF symptoms between December 2010 and October 2011 were prospectively enrolled. Samples were obtained for NGAL and brain natriuretic peptide. Patients were followed up until discharge or for three days, whichever happened first. They were grouped either to have AKI according to “Acute Kidney Injury Network” criteria or not (“no-AKI”). Results: One hundred patients were enrolled. Urine NGAL levels were higher in AKI group (median 31.3 vs. 16.2 ng/mL) (p?<?0.001). Oral furosemide using rates on admission was 60.5% in AKI group, 31.6% in no-AKI group. More AKI developed in patients using less furosemide orally on admission (p?=?0.023). Although the mean furosemide doses were similar on the first day (80?mg), diuretic dose increment was less on the following days in AKI group. Urine NGAL levels with 12?ng/mL cut-off value had sensitivity of 79% and specificity of 67% for predicting AKI. Multiple logistic regression analysis yielded an odds ratio of 10.9 for NGAL levels to predict AKI. Conclusion: Urine NGAL level in decompensated HF patients was not a significant predictor of diuretic dose requirement, but was a good marker for predicting AKI at 12?ng/mL cut-off value.     

Changes in renal markers and acute kidney injury after marathon running

Background: The impact of marathon running on kidney function has not been previously described. Methods: From 425 marathon runners, 13 women and 12 men were randomly selected and cardiovascular magnetic resonance imaging (MRI) and blood/urine biomarkers were performed 4 weeks before (baseline), immediately after (peak), and 24 h after the race (recovery). Results: Participants were 38.7 ± 9.0 years old and completed the marathon in 256.2 ± 43.5 min. A total of 10/25 (40.0%) met the Acute Kidney Injury Network definition of acute kidney injury (AKI) based on a rise in serum creatinine. There were parallel and similar mean rises in serum creatinine and cystatin C from baseline, to peak, and return to normal in recovery. Urine neutrophil gelatinase‐associated lipocalin rose from 8.2 ± 4.0 to 47.0 ± 28.6 and returned to 10.6 ± 7.2 ng/mL, P < 0.0001. Likewise, the mean urinary kidney injury molecule‐1 levels were 2.6 ± 1.6, 3.5 ± 1.6 and 2.7 ± 1.6 ng/mL (P = 0.001). The mean and minimum pre‐ and post‐IVC (inferior vena cava) diameters by MRI were 24.9, 18.8 and 25.3, 17.5 mm, respectively, suggesting that runners were not volume depleted at the first post‐race measurement. Conclusion: Approximately 40% of marathon runners experience a transient rise in serum creatinine that meets criteria of AKI with a parallel elevation of cystatin C, and supportive elevations of neutrophil gelatinase‐associated lipocalin and kidney injury molecule‐1 in the urine. All biomarker elevations resolved by 24 h. These data suggest that AKI with a transient and minor change in renal filtration function occurs with the stress of marathon running. The impact of repetitive episodes of AKI with long‐distance running is unknown.     

肺移植术后早期急性肾损伤的研究进展

急性肾损伤（AKI）是肺移植术后早期常见并发症之一,AKI不仅导致肺移植受者术后近期及远期病死率增加,且显著增加术后远期慢性肾功能不全的发生率。近年来,随着肺移植在中国的迅速发展,肺移植术后早期AKI也引起高度关注。本文对近年来国际上关于肺移植术后早期AKI的诊断、发生情况、危险因素、防治等方面的研究进展进行综述,旨在更好地识别肺移植术后早期AKI相关的危险因素及其不良预后,为临床早期干预提供理论及实践指导。     

Review: Neutrophil gelatinase‐associated lipocalin: A troponin‐like biomarker for human acute kidney injury

Acute kidney injury (AKI) is a common and serious condition, the diagnosis of which currently depends on functional markers such as serum creatinine measurements. Unfortunately, creatinine is a delayed and unreliable indicator of AKI. The lack of early biomarkers of structural kidney injury (akin to troponin in acute myocardial injury) has hampered our ability to translate promising experimental therapies to human AKI. Fortunately, understanding the early stress response of the kidney to acute injuries has revealed a number of potential biomarkers. The discovery, translation and validation of neutrophil gelatinase‐associated lipocalin (NGAL), possibly the most promising novel AKI biomarker, is reviewed. NGAL is emerging as an excellent stand‐alone troponin‐like structural biomarker in the plasma and urine for the early diagnosis of AKI, and for the prediction of clinical outcomes such as dialysis requirement and mortality in several common clinical scenarios. The approach of using NGAL as a trigger to initiate and monitor therapies for AKI, and as a safety biomarker when using potentially nephrotoxic agents, is also promising. In addition, it is hoped that the use of sensitive and specific biomarkers such as NGAL as endpoints in clinical trials will result in a reduction in required sample sizes, and hence the cost incurred. Furthermore, predictive biomarkers like NGAL may play a critical role in expediting the drug development process. However, given the complexity of AKI, additional biomarkers (perhaps a panel of plasma and urinary biomarkers) may eventually need to be developed and validated for optimal progress to occur.     

Urine neutrophil gelatinase associated lipocalin as an early marker of acute kidney injury in hematopoietic stem cell transplantation patients

Abstract

Acute kidney injury (AKI) is common in hematopoietic stem cell transplantation (HSCT) patients with an incidence of 21–73%. Prevention and early diagnosis reduces the frequency and severity of this complication. Predictive biomarkers are of major importance to timely diagnosis. Neutrophil gelatinase associated lipocalin (NGAL) is a widely investigated novel biomarker for early diagnosis of AKI. However, no study assessed NGAL for AKI diagnosis in HSCT patients. We performed further analyses on gathered data from our recent trial to evaluate the performance of urine NGAL (uNGAL) as an indicator of AKI in 72 allogeneic HSCT patients. AKI diagnosis and severity were assessed using Risk–Injury–Failure–Loss–End-stage renal disease and AKI Network criteria. We assessed uNGAL on days ?6, ?3, +3, +9 and +15. Time-dependant Cox regression analysis revealed a statistically significant relationship between uNGAL and AKI occurrence. (HR?=?1.04 (1.008–1.07), p?=?0.01). There was a relation between uNGAL day?+?9 to baseline ratio and incidence of AKI (unadjusted HR?=?1.047 (1.012–1.083), p?<?0.01). The area under the receiver-operating characteristic curve for day?+?9 to baseline ratio was 0.86 (0.74–0.99, p?<?0.01) and a cut-off value of 2.62 was 85% sensitive and 83% specific in predicting AKI. Our results indicated that increase in uNGAL augmented the risk of AKI and the changes of day +9 uNGAL concentrations from baseline could be of value for predicting AKI in HSCT patients. Additionally uNGAL changes preceded serum Cr raises by nearly 2 days.     

Explainable machine learning model for predicting furosemide responsiveness in patients with oliguric acute kidney injury

BackgroundAlthough current guidelines didn’t support the routine use of furosemide in oliguric acute kidney injury (AKI) management, some patients may benefit from furosemide administration at an early stage. We aimed to develop an explainable machine learning (ML) model to differentiate between furosemide-responsive (FR) and furosemide-unresponsive (FU) oliguric AKI.MethodsFrom Medical Information Mart for Intensive Care-IV (MIMIC-IV) and eICU Collaborative Research Database (eICU-CRD), oliguric AKI patients with urine output (UO) < 0.5 ml/kg/h for the first 6 h after ICU admission and furosemide infusion ≥ 40 mg in the following 6 h were retrospectively selected. The MIMIC-IV cohort was used in training a XGBoost model to predict UO > 0.65 ml/kg/h during 6–24 h succeeding the initial 6 h for assessing oliguria, and it was validated in the eICU-CRD cohort. We compared the predictive performance of the XGBoost model with the traditional logistic regression and other ML models.Results6897 patients were included in the MIMIC-IV training cohort, with 2235 patients in the eICU-CRD validation cohort. The XGBoost model showed an AUC of 0.97 (95% CI: 0.96–0.98) for differentiating FR and FU oliguric AKI. It outperformed the logistic regression and other ML models in correctly predicting furosemide diuretic response, achieved 92.43% sensitivity (95% CI: 90.88–93.73%) and 95.12% specificity (95% CI: 93.51–96.3%).ConclusionA boosted ensemble algorithm can be used to accurately differentiate between patients who would and would not respond to furosemide in oliguric AKI. By making the model explainable, clinicians would be able to better understand the reasoning behind the prediction outcome and make individualized treatment.     

Combination of biomarkers for diagnosis of acute kidney injury after cardiopulmonary bypass

Abstract

Novel acute kidney injury (AKI) biomarkers offer promise of earlier diagnosis and risk stratification, but have yet to find widespread clinical application. We measured urinary α and π glutathione S-transferases (α-GST and π-GST), urinary l-type fatty acid-binding protein (l-FABP), urinary neutrophil gelatinase-associated lipocalin (NGAL), urinary hepcidin and serum cystatin c (CysC) before surgery, post-operatively and at 24?h after surgery in 93 high risk patient undergoing cardiopulmonary bypass (CPB) and assessed the ability of these biomarkers alone and in combination to predict RIFLE-R defined AKI in the first 5 post-operative days. Twenty-five patients developed AKI. π-GST (ROCAUC?=?0.75), lower urine Hepcidin:Creatine ratio at 24?h (0.77), greater urine NGAL:Cr ratio post-op (0.73) and greater serum CysC at 24?h (0.72) best predicted AKI. Linear combinations with significant improvement in AUC were: Hepcidin:Cr 24?h?+?post-operative π-GST (AUC?=?0.86, p?=?0.01), Hepcidin:Cr 24?h?+?NGAL:Cr post-op (0.84, p?=?0.03) and CysC 24?h?+?post-operative π-GST (0.83, p?=?0.03), notably these significant biomarkers combinations all involved a tubular injury and a glomerular filtration biomarker. Despite statistical significance in receiver–operator characteristic (ROC) analysis, when assessed by ability to define patients to two groups at high and low risk of AKI, combinations failed to significantly improve classification of risk compared to the best single biomarkers. In an alternative approach using Classification and Regression Tree (CART) analysis a model involving NGAL:Cr measurement post-op followed by Hepcidin:Cr at 24?h was developed which identified high, intermediate and low risk groups for AKI. Regression tree analysis has the potential produce models with greater clinical utility than single combined scores.     

中性粒细胞明胶酶相关脂质运载蛋白对大鼠肾脏缺血再灌注损伤肾小管上皮细胞的保护作用

目的 探讨中性粒细胞明胶酶相关脂质运载蛋白(NGAL)对大鼠缺血再灌注损伤肾脏肾小管上皮细胞凋亡的保护作用及机制.方法 建立大鼠肾脏缺血再灌注模型,雄性SD大鼠随机分为对照组、缺血再灌注模型组、NGAL组 ;HE染色观察3组大鼠肾组织病理变化 ;TUNEL法检测肾小管上皮细胞凋亡 ;实时定量PCR、Western印迹法检测凋亡蛋白fas、bcl-2的表达变化.结果 与缺血再灌注模型组比较,NGAL组肾小管上皮细胞凋亡数量显著减少[(8.6±3.4)/HP比(20.8±3.7)/HP,P＜0.05] ;NGAL组肾组织fas mRNA(2.34±0.51比6.84±2.34,P＜0.05)、fas蛋白(0.65±0.05比0.95±0.08,P＜0.05)表达显著下调,bcl-2蛋白(0.33±0.05比0.24±0.03,P＜0.05)表达显著上调,但bcl-2 mRNA表达无明显改变.结论 NGAL对大鼠缺血再灌注损伤肾小管上皮细胞有保护作用,其作用可能与减少细胞凋亡、改变凋亡蛋白的表达有关.     

白细胞介素18、中性粒细胞明胶酶相关脂质运载蛋白和血清胱抑素C在呼吸衰竭合并急性肾损伤中的变化

目的探讨尿白细胞介素18（interleukin-18,IL-18）、中性粒细胞明胶酶相关脂质运载蛋白（neutrophilgelatinase-associatedlipocalin,NGAL）和血清胱抑素C（cystatinC,Cysc）在呼吸衰竭合并急性肾损伤（acutekidneyinjury,AKI）中的变化。方法收集我院呼吸衰竭患者125例,其中呼吸衰竭并发AKI患者35例（AKI组）,呼吸衰竭未并发AKI患者90例（非AKI组）。检测全血细胞、血清CysC、血肌酐（SCr）、尿素氮（BUN）、血白蛋白水平、血气分析,检测尿NGAL和IL-18水平。结果2组患者间年龄、男女比例、动脉血氧分压、动脉血二氧化碳分压、血红蛋白、白蛋白的差异无统计学意义,而基础有高血压史比例的差异有统计学意义（P〈0．05）。AKI组估算肾小球滤过率（estimatedglomerularfiltrationrate,eGFR）低于非AKI组,差异有统计学意义（P〈0．05）;AKI组SCr、BUN、血清CysC、尿NGAL和II,18高于非AKI组,差异有统计学意义（P〈0．05）;Pearson相关分析显示AKI组尿IL-18、NGAL及血清CysC均与SCr具有相关性,与eGFR也具有相关性。多因素Logistic回归分析显示尿IL-18、NGAL、血清CysC升高是呼吸衰竭发生AKI的独立危险因素。结论尿IL-18、NGAL和血清CysC对诊断呼吸衰竭合并AKI有较高的准确性。     

Pilot double-blind, randomized controlled trial of short-term atorvastatin for prevention of acute kidney injury after cardiac surgery

Aim: To test whether short‐term perioperative administration of oral atorvastatin could reduce incidence of postoperative acute kidney injury (AKI) in cardiac surgical patients. Methods: We conducted a double‐blind, randomized controlled trial in 100 cardiac surgical patients at increased risk of postoperative AKI. Patients were randomized to atorvastatin (40 mg once daily for 4 days starting preoperatively) or identical placebo capsule. Primary outcome was to detect a smaller absolute rise in postoperative creatinine with statin therapy. Secondary outcomes included AKI defined by the creatinine criteria of RIFLE consensus classification (RIFLE R, I or F), change in urinary neutrophil gelatinase‐associated lipocalin (NGAL) concentration, requirement for renal replacement therapy, length of stay in intensive care, length of stay in hospital and hospital mortality. Results: Study groups were well matched. For each patient maximal increase in creatinine during the 5 days after surgery was assessed; median maximal increase was 28 µmol/L in the atorvastatin group and 29.5 µmol/L in the placebo group (P = 0.62). RIFLE R or greater occurred in 26% of patients with atorvastatin and 32% with placebo (P = 0.65). Postoperatively urine NGAL changes were similar (median NGAL : creatinine ratio at intensive care unit admission: atorvastatin group 1503 ng/mg, placebo group 1101 ng/mg; P = 0.22). Treatment was well tolerated and adverse events were similar between groups. Conclusion: Short‐term perioperative atorvastatin use was not associated with a reduced incidence of postoperative AKI or smaller increases in urinary NGAL. (ClinicalTrials.gov NCT00910221).     

Investigation of urinary neutrophil gelatinase associated lipocalin (NGAL) for early diagnosis of acute kidney injury after percutaneous nephrolithotomy

Introduction

Percutaneous nephrolithotomy (PCNL) could be mentioned as the most important treatment of choice for kidney staghorn stones. Previous publications reported that the novel biomarker urinary neutrophil gelatinase-associated lipocalin (NGAL) activity significantly increases in acute kidney injury (AKI) but there is not many published articles related to increase of NGAL after PCNL procedure.

血清CysC、UmAlb、Scr在脓毒症合并急性肾损伤患者中的表达及疾病预测价值

目的:研究血清胱抑素C(CysC)、尿微量白蛋白(UmAlb)、血肌酐(Scr)在脓毒症合并急性肾损伤(AKI)患者中的表达及疾病预测价值。方法:选择2019年10月至2020年10月间宜昌市夷陵医院收治的117例脓毒症患者纳为研究对象,根据患者是否并发AKI,将其分为AKI组(51例)与非AKI(NAKI)组(66例...     

住院患者急性肾损伤的发病情况调查

目的 了解我国综合性医院住院患者急性肾损伤（AKI）的发病率、病因构成、预后，以及肾功能受损对住院费用和住院时间的影响。 方法 通过调查2004年9月1日至2005年8月31日复旦大学附属中山医院住院患者的肾功能检测结果，筛检出AKI患者，进行病史复习，总结分析患者的临床特征及其转归、肾功能受损的性质、导致肾功能不全的基础疾病等。 结果 观察期间共有住院患者37 365例次，其中1263例患者住院期间发生AKI，发病率为3.38%。观察期间住院患者总病死率为1.52%，其中AKI患者病死率为18.57%，经校正后AKI对患者住院病死率的OR值为10.08（P < 0.01）。Logistic回归分析提示高龄、Scr上升的百分比是AKI患者死亡的危险因素。 结论 住院患者AKI的发病较常见。患者Scr上升26.5 μmol/L即可增加死亡的风险，增加住院费用，延长住院天数。患者的预后同肾脏受损的程度相关，其病死率随Scr上升百分数的增加而增加